A Phase II/III Trial of Rifampin, Ciprofloxacin, Clofazimine, Ethambutol, and Amikacin in the Treatment of Disseminated Mycobacterium Avium Infection in HIV-Infected Individuals.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000641
First received: November 2, 1999
Last updated: March 29, 2012
Last verified: March 2012
  Purpose

To compare the effectiveness and toxicity of two combination drug treatment programs for the treatment of disseminated Mycobacterium avium infection in HIV seropositive patients. [Per 03/06/92 amendment: to evaluate the efficacy of azithromycin when given in conjunction with either ethambutol or clofazimine as maintenance therapy.] Disseminated M. avium infection is the most common systemic bacterial infection complicating AIDS in the United States. The prognosis of patients with disseminated M. avium is extremely poor, particularly when it follows other opportunistic infections or is associated with anemia. Test tube studies and clinical data indicate that the best treatment program may include clofazimine, ethambutol, a rifamycin derivative, and ciprofloxacin. Test tube and animal studies indicate that amikacin is a bactericidal (bacteria destroying) drug that works better when used with ciprofloxacin. Its role in treatment programs is a key issue because of toxicity and because it must be administered parenterally (by injection or intravenously).


Condition Intervention Phase
Mycobacterium Avium-intracellulare Infection
HIV Infections
Drug: Ciprofloxacin hydrochloride
Drug: Ethambutol hydrochloride
Drug: Amikacin sulfate
Drug: Azithromycin
Drug: Rifampin
Drug: Clofazimine
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II/III Trial of Rifampin, Ciprofloxacin, Clofazimine, Ethambutol, and Amikacin in the Treatment of Disseminated Mycobacterium Avium Infection in HIV-Infected Individuals.

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 90
Study Completion Date: December 1994
Detailed Description:

Disseminated M. avium infection is the most common systemic bacterial infection complicating AIDS in the United States. The prognosis of patients with disseminated M. avium is extremely poor, particularly when it follows other opportunistic infections or is associated with anemia. Test tube studies and clinical data indicate that the best treatment program may include clofazimine, ethambutol, a rifamycin derivative, and ciprofloxacin. Test tube and animal studies indicate that amikacin is a bactericidal (bacteria destroying) drug that works better when used with ciprofloxacin. Its role in treatment programs is a key issue because of toxicity and because it must be administered parenterally (by injection or intravenously).

Patients undergo an initial 2-week observation period (days 1 - 14) during which time baseline evaluations are performed and type and severity of symptoms are monitored. Eligible patients are randomized on day 15 to one of two treatment programs: (1) ciprofloxacin, clofazimine, ethambutol, and rifampin (all taken orally), or (2) the same four drugs plus amikacin. Only patients for whom blood cultures obtained on either day 1 or day 14/15 are positive by week 6 continue on study drugs. Patients receive combination therapy for 24 weeks. Patients may have an indwelling central venous catheter in place for long-term administration of intravenous drug. PER 03/06/92 AMENDMENT: Newly enrolled patients who demonstrate a complete or partial clinical response at the end of study week 10 (8 weeks of drug therapy) discontinue their current regimen and begin maintenance therapy with azithromycin plus either ethambutol or clofazimine for an additional 24 weeks. Patients who do not demonstrate a response at study week 10 are discontinued from all study therapy. Patients enrolled on earlier versions of the protocol who have surpassed study week 16 (14 weeks of drug therapy) continue treatment with their originally assigned regimen through study week 26; those who have not surpassed study week 16 are considered for inclusion in the maintenance phase of the study.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Zidovudine (AZT) and didanosine (ddI). Dideoxycytidine (ddC), EPO, and other experimental therapies granted Treatment IND or Expanded Access status, with the exception of rifabutin.
  • Concurrent therapies (acute and maintenance) for opportunistic infections not specifically prohibited.

Concurrent Treatment:

Allowed:

  • Interferon-alfa.

Patients must have the following:

  • HIV infections or diagnosis of AIDS as per CDC classification.
  • Mycobacterium avium isolated from blood.
  • Capability of signing an informed consent, or consent of guardian if < 18 years of age.
  • Ability and willingness to participate in all components of the study and receive all study therapies.

Prior Medication:

Allowed:

  • Interferon-alfa.
  • Single drug prophylaxis for Mycobacterium avium or M. tuberculosis within the previous 4 weeks.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

Treatment Phase:

  • Known or suspected allergy to any of the study medications. Severe hearing loss.

Maintenance Phase:

  • Severe hearing loss. Hypersensitivity to macrolides. Intolerance to ethambutol and clofazimine.

Concurrent Medication:

Excluded:

  • Acute therapy for other opportunistic infections at time of study entry.
  • Nephrotoxic agents such as amphotericin B, intravenous vancomycin, or foscarnet during the first 4 weeks of study therapy without specific exemption from one of the protocol chairs. Antacids within 2 hours of ingestion of study drugs.
  • Immunomodulators (except interferon-alfa) and other antimycobacterial drugs (including quinolones and aminoglycosides).
  • All experimental therapies (except ddI, ddC, and other experimental agents granted "Treatment IND" or "expanded access" status) will be prohibited (specific exemptions must be obtained from one of the protocol chairs).

Patients with the following are excluded:

  • Known or suspected allergy to any of the study medications. Cannot take drugs orally.
  • Severe hearing loss, at the discretion of the investigator.

Prior Medication:

Excluded:

  • Antimycobacterial drugs (including azithromycin, clarithromycin, rifamycins, quinolones, and aminoglycosides) or immunomodulators (except interferon-alfa) within 4 weeks prior to entry, except single-drug prophylaxis specifically allowed.

History of unreliable drug intake.

  • Inability to cooperate in the testing procedures.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000641

Locations
United States, California
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States, 90502
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 46202
United States, Missouri
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, United States
Washington U CRS
St. Louis, Missouri, United States
United States, New Jersey
NJ Med. School CRS
Newark, New Jersey, United States, 07103
United States, New York
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
NYU Med. Ctr., Dept. of Medicine
New York, New York, United States
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 27599
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, United States, 27710
Regional Center for Infectious Disease, Wendover Medical Center CRS
Greensboro, North Carolina, United States
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 45267
Case CRS
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Pitt CRS
Pittsburgh, Pennsylvania, United States, 15213
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98122
Sponsors and Collaborators
Investigators
Study Chair: DM Parenti
Study Chair: J Ellner
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000641     History of Changes
Other Study ID Numbers: ACTG 135, 11110
Study First Received: November 2, 1999
Last Updated: March 29, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Rifampin
Mycobacterium avium-intracellulare Infection
Drug Evaluation
Drug Therapy, Combination
Ethambutol
Clofazimine
Acquired Immunodeficiency Syndrome
Amikacin
Azithromycin
Ciprofloxacin

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Mycobacterium Infections
Mycobacterium avium-intracellulare Infection
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Mycobacterium Infections, Nontuberculous
Ciprofloxacin
Rifampin
Ethambutol
Amikacin
Clofazimine
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014